This invention relates generally to methods for synthesizing cyclohexene dimethanol or cyclohexane dimethanol compounds, and, more particularly, to methods for obtaining cyclohexene dimethanol or cyclohexane dimethanol compounds in high yields and having high purity while eliminating certain costly and time-intensive procedures associated with solvent extraction and product recrystallization.
Cyclohexene dimethanol compounds, such as 3-cyclohexene-1,1-dimethanol, have been used as monomers for synthesizing high performance active barrier polymers which are currently under intensive development as next generation food and beverage packaging technology. (See, for example, PCT Publication No. WO 99/48963, assigned to Chevron Chemical Co.). A prior synthesis approach for producing such compounds is based on the Cannizzaro reaction. For example, in synthesizing 3-cyclohexene-1,1-dimethanol by this approach, two mole of formaldehyde reacts with one mole of tetrahydrobenzaldehyde in the presence of one mole of base, e.g., sodium hydroxide or potassium hydroxide, in an aqueous alcoholic solution. The reaction presumably follows the course indicated by the following: 
This process has typically involved a reaction stage in aqueous or aqueous-alcoholic medium, followed by a purification stage that requires multiple extraction steps with organic solvent, a distillation step and a recrystallization step from a suitable organic solvent. In one example (H. E. French and D. M. Gallagher, JACS 1942, p 1497), a reaction was conducted in an aqueous-alcoholic medium in the presence of potassium hydroxide at 70xc2x0 C. The purification stage involved the extraction of the reaction medium with ether, followed by distillation to remove the solvent. The crude product was an oil residue that solidified upon standing over time. Recrystallization of the product gave a yield reported to be in the range of 50-60%. The melting point, which served as an indication of product purity, was reported to be 92.5xc2x0 C.
In a separate report (Klaus Bruns and Jens Conard, Tetrahydron, Vol. 35, p2523, 1979), a reaction stage was carried out in aqueous sodium hydroxide, while the purification stage involved multiple extractions with methylisobutylketone, a specialty solvent. The crude yield, reported to be 92%, was based on the residue from the evaporation of the solvent, and no further purification was described. We performed this procedure and found that it does not provide a level of purity sufficient for making polymerization grade 3-cyclohexene-1,1-dimethanol. Moreover, further purification steps necessary to achieve a sufficient level of purity led to unacceptably low yields.
When considering the commercial scale production of 3-cyclohexene-1,1-dimethanol and other cyclohexene dimethanol or cyclohexane dimethanol compounds, the involvement of large quantities of expensive organic solvents and long cycle times for multiple organic/aqueous extractions and crystallizations make the prior processes undesirable from both a material and operational cost standpoint. Indeed, the number of operation units, such as organic solvent storage tanks, mixing tanks and distillation units contribute significantly to the overall cost of producing these compounds. In light of this, significant benefits could be realized by eliminating one or more of the operational steps associated with product extraction and/or recrystallization.
The present invention overcomes, or at least reduces the effects of, one or more of the aforementioned problems.
According to a first aspect of the present invention, a method is provided for producing a cyclohexene dimethanol or a cyclohexane dimethanol compound, comprising:
(a) adding a base solution to a formaldehyde solution to form a formaldehyde/base solution;
(b) adding an aldehyde to the formaldehyde/base solution to form a reaction solution; and
(c) recovering cyclohexene dimethanol or cyclohexane dimethanol product from said reaction solution.
According to another aspect of the invention, a method is provided for producing a cyclohexene dimethanol or a cyclohexane dimethanol compound, comprising:
(a) adding a base solution to a formaldehyde solution to form a formaldehyde/base solution;
(b) adding an aldehyde to the formaldehyde/base solution to form a reaction solution;
(c) heating the reaction solution to a temperature about 70xc2x0 C. or less;
(d) cooling the reaction vessel contents to between about 10xc2x0 C. and 30C; and
(e) recovering cyclohexene dimethanol or cyclohexane dimethanol product from said reaction solution.
According to another aspect of the invention, a method is provided for producing 3-cyclohexene-1,1-dimethanol having a yield greater than about 80% and a purity greater than about 95%, comprising:
(a) adding a base solution to a formaldehyde solution to form a formaldehyde/base solution, wherein the temperature of the formaldehyde/base solution is maintained between about 10xc2x0 C. and about 20xc2x0 C. during addition of said base solution;
(b) adding a tetrahydrobenzaldehyde, to the formaldehyde/base solution to form a reaction solution, wherein the temperature of the reaction solution is maintained between about 10xc2x0 C. and about 20xc2x0 C. during addition of said tetrahydrobenzaldehyde;
(c) maintaining the temperature of the reaction solution between about 15xc2x0 C. and about 25xc2x0 C. for at least about 4 hours following addition of said tetrahydrobenzaldehyde;
(d) heating the reaction solution to a temperature between about 50xc2x0 C. and about 60xc2x0 C. for at least about 0.5 hours to about 2 hours;
(e) cooling the reaction vessel contents to between about 10xc2x0 C. and about 30xc2x0 C.; and
(f) recovering crystalline-form 3-cyclohexene-1,1-dimethanol product from said reaction solution.
Illustrative embodiments of the invention are described below. In the interest of clarity, not all features of an actual implementation are described in this specification. It will of course be appreciated that in the development of any such actual embodiment, numerous implementation-specific decisions must be made to achieve the developers"" specific goals, such as compliance with system-related and business-related constraints, which will vary from one implementation to another. Moreover, it will be appreciated that such a development effort might be complex and time-consuming, but would nevertheless be a routine undertaking for those of ordinary skill in the art having the benefit of this disclosure.
In order to develop an economically viable process for making cyclohexene dimethanol or cyclohexane dimethanol compounds, we have investigated alternative processes effective for eliminating organic solvent-based extraction and/or recrystallization steps during the purification stage of the process. In addition, we also sought to further improve product yield while- maintaining sufficient product purity.
According to the present invention, high purity cyclohexene dimethanol or cyclohexane dimethanol can be obtained in a crystalline form by controlling certain process parameters during the progress of the synthesis reaction. In particular, we have found that by controlling the rate of addition of certain reagents and the temperature profile during the reaction stage, cyclohexene dimethanols or cyclohexane dimethanols can be produced having high purity while eliminating some or all of the steps of solvent extraction and/or recrystallization required by prior synthesis methods. In contrast to prior methods, the present invention provides high purity crystalline-form product that can be obtained directly from the reaction medium.
According to the present invention, a cyclohexene dimethanol or a cyclohexane dimethanol is synthesized by reacting formaldehyde with an aldehyde, preferably an aldehyde with from 2 to about 20 carbon atoms, more preferably tetrahydrobenzaldehyde or cyclohexane carboxyaldehyde, in the presence of base in an aqueous or aqueous-alcoholic solution. The reaction vessel employed, e.g., a 4-neck flask or the like, is not critical. The reaction vessel can be suitably equipped with a mechanical stirrer or some other means for effecting agitation of the reaction medium, a thermometer, a nitrogen circulation, an external cooling source, such as a cooling bath, and/or any other feature necessary or desired for a given application.
The process is typically performed by first charging a reaction vessel with formaldehyde. To this formaldehyde solution, a base solution is added, preferably under some form of agitation. The base will typically be an aqueous base solution, for example a sodium hydroxide or potassium hydroxide solution. The base solution can also comprise an aqueous-alcoholic solution, if desired, comprising an alcohol such as propanol, ethanol, butanol or the like, in addition to an aqueous component. Theoretically, the amount of base required to be added to the formaldehyde to ensure substantial completion of the synthesis reaction that will follow is 1 equivalent of base to 2 equivalents of formaldehyde. Of course, for practical reasons, the relative amounts of these and other components of the reaction may be varied depending on the particular implementation of the invention.
Under basic conditions, formaldehyde can undergo a polymerization reaction that is undesirable in the context of this synthesis reaction since it represents a source for contaminating by-products that can degrade both the yield and purity of the desired product. Therefore, it is preferred that during the addition of the base solution to the formaldehyde solution, the temperature of the reaction vessel contents are maintained sufficiently low so as to minimize formaldehyde polymerization. This can most readily be achieved by controlling the temperature of the reaction vessel contents, for example using a suitable cooling source such as a cooling bath or another cooling means available in the art. Moreover, the rate of addition of the base solution to the formaldehyde solution can contribute to this formaldehyde polymerization by increasing the temperature of the reaction solution. Thus, in addition to the use of an external cooling source, the rate of addition of the base solution to the formaldehyde solution is preferably controlled as well.
Therefore, in certain illustrative embodiments of the present invention, an external cooling source is used to maintain the temperature of the reaction vessel contents between about 5xc2x0 C. and about 40xc2x0 C., more preferably between about 10xc2x0 C. and about 30xc2x0 C., and most preferably between about 10xc2x0 C. and about 20xc2x0 C., during the addition of the base solution to the formaldehyde solution, and the rate of addition of the base solution to the formaldehyde solution is controlled such that the temperature of the reaction vessel contents throughout this addition is maintained within these desired temperature ranges.
After the base solution has been added, an aldehyde is introduced into the reaction vessel, preferably under some form of agitation. In one preferred embodiment of the invention, the aldehyde is a tetrahydrobenzaldehyde, more preferably 1,2,5,6-tetrahydrobenzaldehyde, used in a reaction for producing 3-cyclohexene-1,1-dimethanol. It will be recognized by the skilled artisan that many structural features of the tetrahydrobenzaldehyde starting material can be varied, and that this will dictate the structural features of the cyclohexene dimethanol produced therefrom. Thus, if it is desired to produce a cyclohexene dimethanol containing, for example, substitutions at some point along the cyclohexene ring of the product molecule, this can be achieved by selecting the correspondingly substituted tetrahydrobenzaldehyde starting material for use in the reaction.
Alternatively, the aldehyde can be a cyclohexane carboxyaldehyde and can be used in a reaction for producing cyclohexane-1,1-dimethanol. Again, it will be recognized by the skilled artisan that many structural features of the cyclohexane carboxyaldehyde starting material can be varied, and that this will dictate the structural features of the cyclohexane dimethanol produced therefrom. Thus, if it is desired to produce a cyclohexane dimethanol containing, for example, substitutions at some point along the cyclohexane ring of the product molecule, this can be achieved by selecting the correspondingly substituted cyclohexane carboxyaldehyde starting material for use in the reaction.
In a theoretical sense, 1 equivalent of aldehyde is added for every 2 equivalents of formaldehyde that was added previously to the reaction vessel. However, as will be recognized by the skilled artisan, these are not absolute limitations on the practice of this invention. Rather, the precise amounts of the components used in the synthesis procedure described herein can be varied, as desired, to best suit the needs of a given implementation of this process.
As during the base addition step discussed above, temperature control has been found to be important during addition of the aldehyde to the reaction solution. This temperature control is particularly important in allowing effective crystallization of high purity product directly from the reaction solution. Therefore, an external cooling source is preferably used to maintain the temperature of the reaction vessel contents between about 5xc2x0 C. and about 40xc2x0 C., more preferably. between about 10xc2x0 C. and about 30xc2x0 C., and most preferably between about 10xc2x0 C. and about 20xc2x0 C., during addition of the aldehyde to the formaldehyde/base solution. Moreover, the rate of addition of the aldehyde to the formaldehyde/base solution is preferably controlled such that the temperature of the reaction vessel contents throughout this addition is maintained within these desired temperature ranges.
During the addition of aldehyde under these conditions, some crystalline product develops after an initial emulsion stage. Agitation is preferably maintained during this addition to ensure a largely aggregate-free suspension of crystalline product in the reaction medium. This crystalline product may be recovered, as desired, at this or any stage hereafter.
However, it may be preferred that after addition of the aldehyde is complete, the temperature of the reaction vessel contents is maintained between about 10xc2x0 C. and about 30xc2x0 C., preferably between about 15xc2x0 C. and about 25xc2x0 C., until the reaction exotherm is dissipated. Illustratively, the reaction vessel contents are maintained at such temperatures for about 1-2 hours, preferably for about 3-4 hours, or more.
At a point after addition of the aldehyde is complete and/or after the reaction vessel contents have been maintained at a temperature between about 10xc2x0 C. and about 30xc2x0 C., preferably between about 15xc2x0 C. and about 25xc2x0 C., until the reaction exotherm has largely dissipated, the reaction vessel contents can be heated to a temperature up to about 70xc2x0 C., preferably between about 40xc2x0 C. and about 70xc2x0 C., more preferably between about 50xc2x0 C. and about 60xc2x0 C., for several minutes to several hours, in order to facilitate the reaction of any unreacted formaldehyde and aldehyde. Higher temperatures allow the reaction to proceed more rapidly, but temperatures greater than about 70xc2x0 C. lead to unacceptably high levels of side products.
Subsequent to this heating, the reaction vessel contents are then allowed to cool, typically to a temperature in the range of about 15xc2x0 C. to about 25xc2x0 C., in order to effect crystallization of product remaining in solution. Preferably, this cooling is performed under some form of agitation in order to prevent aggregation of the crystalline product.
By practice of the disclosed invention, a high-purity crystalline product can be obtained. The crystalline product can be recovered from the reaction solution by any of a variety of techniques known in the art, e.g., by suction filtration, centrifugation, etc. The material that is collected by filtration will typically in the form of a wet-cake that is then dried to obtain solid, crystalline product. If desired, one or more rinses of the wet-cake with water or an aqueous-based solution can be used to help remove any impurities that may have remained in the crystalline product. For example, these rinses can involve first immersing the wet-cake in water without vacuum and allowing it to sit for several minutes or hours before vacuum is applied to remove the rinse solution.
The wet-cake can be left at ambient temperature to dry or can be dried at an elevated temperature, for example in a vacuum oven, a tumble dryer, or the like. The wet-cake can be dried at essentially any elevated temperature provided it does not exceed the melting temperature of the cyclohexene dimethanol or cyclohexane dimethanol product. Of course, it will be understood that the drying time necessary to dry the wet-cake will be inversely related to the drying temperature employed, and, thus, these conditions can be varied as a matter of operational convenience.
The purity of the product obtainable by this process is typically greater than 85%, preferably greater than about 95%, more preferably greater than about 99%. The high purity of the cyclohexene dimethanol product obtainable by practice of the present invention was confirmed by both melting point (m.p. greater than 92-93xc2x0 C.) and GC analysis ( greater than 99%).
The yield of the product is generally greater than about 70%, more preferably greater than about 80%. In addition, yield can be further improved if product remaining in the filtrate is extracted with a suitable organic solvent. In this way, an additional quantity of product can be recovered. Since this can be done on an accumulative basis from lot to lot, and the quantity of organic solvent used is very small, and recyclable, this will further improve the economy of the process.
Thus, in another embodiment, the quantity of product remaining in the filtrate is solvent extracted, for example with methylisobutylketone, or another suitable organic solvent. The organic phase can be condensed and the solid obtained therefrom is recrystallized, for example from acetone or ethanol, to yield additional pure product. Total product yields of 85% or more can be achieved according to this embodiment of the invention.